Effects of Levosimendan on Hydrogen Peroxide Induced Contraction in Human Saphenous Vein
Pharmacology and Pharmacy
Aim: Increased oxidative stress plays important roles in vascular dysfunction in patients undergoing coronary artery bypass graft surgery. Hydrogen peroxide (H 2 O 2 ) is used as an experimental model for oxidative stress. The present study was designed to assess the effects of levosimendan pretreatment on the contractile effects induced by H 2 O 2 in human saphenous vein (HSV) segments. Methods: We studied H 2 O 2 induced contractions of isolated HSV mounted in standard tissue baths. H 2 O 2
... ue baths. H 2 O 2 (10 -6 -10 -3 M) was added cumulatively to the organ bath. Concentration-response curves to H 2 O 2 were repeated in the presence of levosimendan (10 -8 M). In the second series of experiments, strips were contracted with 5-HT (10 -5 M). When the contraction reached a stable plateau, H 2 O 2 was administrated cumulatively into the organ bath. The same procedure was conducted in the presence of levosimendan. Results: Pretreatment of the SV strips with levosimendan significantly reduced the contractile response to each concentration of H 2 O 2 . 5-HT produced contractions in SV strips. Further treatment of these strips with H 2 O 2 resulted in statistically significant concentration-dependent increases in tension. Preincubation of the tissues with levosimendan did not significantly influence the maximum amplitude of the 5-HT-induced tone but inhibited the contractile effect of H 2 O 2 on the 5-HT-induced contraction. Conclusion: Pretreatment of HSV with clinical concentrations of levosimendan inhibits the vasoconstriction caused by oxidative stress, indicating its potential preventive effect against oxidative stress induced graft spasm.